The lab studies the quantitative operation of the systems that living cells use to sense, represent, transmit, and act upon information to make appropriate responses. One system under study is a prototypic cell signaling system in budding yeast, the pheromone response system. When appropriate (which is frequently) experimental work proceeds in concert with efforts to account for observed quantitative behaviors by simulation. Work has recently led to some general insights into the information carried by cell signaling systems and how that is controlled. This work is benefitting from a deeper association with control theory and theorists. A recent outcome of this association is design and construction intracellular devices that can give much more precise control of chemically tuned gene expression, with one explicit goal being to give good gene control in mammalian cells to researchers worldwide.
Lab has extended similar work to systems operating in single cells of tissues in a metazoan, Caenorhabditis elegans. Because the lab studies system operation in single cells, we also study the causes and consequences of cell-to-cell variation in function of these systems, and the still-mysterious persistent cell physiological states that underlie much of this variation. Differences in these physiological states can have significant effects on the function of the organism that continue over the organism's life.
Work requires continual development and refinement of experimental and computational methods. One area of continual development is rapid means to generate new DNA constructions and make desired changes to the genomes of yeast and higher cells. Another is development of intracellular reporters that can quantify particular molecular events in living cells, together with microscopic, flow cytometric, and computational means to read the output of these reporters. We expect that this technology development will continue to finds application to other biological problems including cancer research and drug screening.
The lab also includes experimental social science component. Some of this work continues under the aegis of the Center for Biological Futures, a two-year pilot project that brought together biologists with scholars in the social sciences and humanities, including anthropologists and philosophers, to better understand how biological knowledge and capability are shaping human affairs in the 21st century. This work included a significant collaboration with investigators at the University of Washington, in the project Biological Futures in a Globalized World. Brent and other lab members are frequently able to participate in government and other advisorial settings to help shape the overall course of future research, and all lab members are encouraged to consider how the outcomes of their research and the ongoing increases in biological knowledge and capability might shape, and should shape, human affairs.
12 June 2016
ISAC/ CTYO 2016 meeting in Seattle
At this meeting Brent gave a "State of the art lecture" titled "Quantitative physiology of living single-cells: subtle pleasures and future promise". The hope was to give the listeners a heads up on how one can use single cell measurements to define some non-obvious physiological states (including having high gene expression power or G) in yeast and worm cells, and the consequences of those states.
Colman-Lerner, A., Gordon, A., Serra, E., Chin, T., Resnekov, O., Endy, D., Pesce, G. and Brent, R. (2005) Regulated cell-to-cell variation in a cell fate decision system. Nature. 437, 699-706
6 June 2016
Second phasor plotting paper published
Our second paper with the Houston lab at NMSU, on use of phasors and pseudophasors in flow cytometry, is now out. In time resolved flow cytometry, we expect these methods will be as powerful as they are in microscopy.
Cao R, Jenkins P, Peria W, Sands B, Naivar M, Brent R, Houston JP. Opt Express. 2016 Jun 27;24(13):14596-607. doi: 10.1364/OE.24.014596. PMID: 27410612
31 March 2016
Mendenhall starts own lab at UW
Alex Mendenhall starts a tenure track faculty appointment in the Department of Pathology at UW School of Medicine. The department is distinguished by the depth of its expertise on aging, making it something of a dream job for him. Will link to his lab website as soon as its up. Mendenhall did very well here, and he will be deeply missed.
15 February 2016
Single cell physiological states and aging
Alex Mendenhall, Monica Driscoll, and Brent have a closely argued piece out in Aging Cell about how scientists can use single-cell measures of physiological state can contribute to an understanding of organismic aging (and response to perturbations) in adult organisms. A major reason for this article was to put forward, particularly for aging researchers, but also for researchers seeking to understanding organismic physiology, logically consistent and eventually computable definitions of concepts such as "physiological state" We come down pretty strongly on the viewpoint that to view aging as the execution of a "genetic program" in the same sense that embryonic development clearly is the working out of genetic program. We hope to provoke discussions about and lay groundwork for measurement of single cell physiological variables through the entire developmental and adult trajectory of organisms. We also hope to give the aging community some new ideas to accept or criticize.
Mendenhall A, Driscoll M, Brent R. Using measures of single-cell physiology and physiological state to understand organismic aging. Aging Cell. 2016 Feb;15(1):4-13. doi: 10.1111/acel.12424. Epub 2015 Nov 29. Review. PMID: 26616110
4 January 2016
post-Cohen-Boyer DNA assembly now out
Overview of post Cohen-Boyer methods for single segment cloning and for multisegment DNA assembly. Sands B, Brent R. Curr Protoc Mol Biol. 2016 Jan;113:3.26.1-3.26.20. Epub 2016 Jan 4. PMID: 27152131
With the overview now published, the plan is to publish Bryan's latest assembly methods as a separate paper later in 2016